there is little data on PON after ASC, but even with a response, I would not be confident about durability
I would allograft ASAP before he blasts off

Hi.
I want to have your thoughts on the same case we discussed a while ago. The patient is now 20 yo. He has failed with three TKIs, started asciminib in Apr 2022, and maintained the PCR in 0.1-0.2%IS range but attained MMR only a few times. I previously said he was on 40 mg BID, but actually, he was on 80 mg QD.
He came back for follow up recently and PCR went up to 2%. I asked our BMT team to do donor search again and now, they have an unrelated donor with 9/10 match. (Previously, there was only haplo.) I have thought about switching asciminib to ponatinib, but I think the same thing will likely happen; he will respond, but will lose molecular remission after a while.

With a better donor option, I am thinking about taking him to HSCT now.
I would appreciate your suggestions

Nobuko Hijiya
Columbia University, NYC

Hi Nobuko,

Very difficult case. It looks like he will not sustain a good molecular response to asciminib but I would probably watch for a few more months to be sure. If he is losing response to asciminib, which looks likely, and given the less than ideal donor, I would be thinking about ponatinib (45 mg/day with reduction to 15mg/day if/when he achieves MR2) as a last chance before considering the transplant option. Before stopping the asciminib it would be important to screen for kinase domain and myristoyl site mutations. Any single mutation should not represent a problem for ponatinib but if he has compound mutations, ponatinib may not be a good option – depending on the actual mutations.

Cheers - Tim

Dear Nobuko,

I suggest to maintain him on asciminb, simplify at 80mg QD and from time to time if fluctuation stable, ask for KD mutation analysis.

Best regards,

Delphine Rea

The patient is a 19 yo male.  He was initially diagnosed in 2017.  He came to us from another center after he failed imatinib, dasatinib and nilotinib.    There is no doubt about his compliance.    He has responded to each TKI initially, then, the level went up.   He did not have TKD mutations.   When he was referred to our BMT team, I suggested asciminib as he was18 yo. (Asciminib has not been approved for children.)  He started standard dose 40 mg BID in April 2022 and achieved molecular remission.   He achieved MR3 in 4 months but there are some up and downs up to 0.5%4/12/22       10.3% (prior to asciminib)5/31/22       3.4%8/19/22       0.13%11/18/22     0.039% (MR3)3/9/23         0.065%6/27/23       0.58% (lost MR3)7/10/23       0.375%7/28/23       0.098% (regained MR3)8/29/23      0.028%  (the lowest so far)9/25/23      0.108%10/25/23    0.21%The best donor option is haplo.   What do you recommend?
I appreciate your thoughts.  
Nobuko

Nobuko Hijiya, MD
Pediatric Oncology
Columbia University Irving Medical Center